Evidence map›Paper›PMID 21123744›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2010

Elements between the IgH variable (V) and diversity (D) clusters influence antisense transcription and lineage-specific V(D)J recombination.

Cosmas C Giallourakis, Andrew Franklin, Chunguang Guo, Hwei-Ling Cheng, Hye Suk Yoon, Michael Gallagher, Thomas Perlot, Milena Andzelm, Andrew J Murphy, Lynn E Macdonald and 2 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.0field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 35 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Alterations in chromatin at antigen receptor loci define lineage progression during B lymphopoiesis.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  5. Article
  6. Sequential activation and distinct functions for distal and proximal modules within the IgH 3' regulatory region.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
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  18. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Cosmas C GiallourakisDepartment of Genetics, The Howard Hughes Medical Institute, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Andrew Franklin
Chunguang Guo
Hwei-Ling Cheng
Hye Suk Yoon
Michael Gallagher
Thomas Perlot
Milena Andzelm
Andrew J Murphy
Lynn E Macdonald
George D Yancopoulos
Frederick W Alt
Harvard University · USHoward Hughes Medical Institute · USRegeneron (United States) · US

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Ramnik J Xavier · 1991 to 2026
$35.3M
Mechanisms that Control IgH Variable Region Exon AssemblyR01AI020047 · NIAID · IMMUNE DISEASE INSTITUTE, INC. · PI ALT, FREDERICK W. · 1985 to 2025
$14.1M
Genetic Analysis of VDJ Recombination RegulationK08AI070839 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI GIALLOURAKIS, COSMAS C · 2006 to 2010
$647k
ASSEMBLY AND EXPRESSION OF IG VARIBLE REGION GENESR37AI020047 · NIAID · IMMUNE DISEASE INSTITUTE, INC. · PI ALT, FREDERICK W · 1991 to 2000
$323k
Howard Hughes Medical InstituteNIAID NIH HHS AI20047NIAID NIH HHS K08 AI070839NIAID NIH HHS R01 AI020047NIAID NIH HHS R37 AI020047NIDDK NIH HHS P30 DK043351NIGMS NIH HHS T32 GM007753
6 · The paper itself

Abstract

Ig and T-cell receptor (TCR) variable-region gene exons are assembled from component variable (V), diversity (D) and joining (J) gene segments during early B and T cell development. The RAG1/2 endonuclease initiates V(D)J recombination by introducing DNA double-strand breaks at borders of the germ-line segments. In mice, the Ig heavy-chain (IgH) locus contains, from 5' to 3', several hundred V(H) gene segments, 13 D segments, and 4 J(H) segments within a several megabase region. In developing B cells, IgH variable-region exon assembly is ordered with D to J(H) rearrangement occurring on both alleles before appendage of a V(H) segment. Also, IgH V(H) to DJ(H) rearrangement does not occur in T cells, even though DJ(H) rearrangements occur at low levels. In these contexts, V(D)J recombination is controlled by modulating substrate gene segment accessibility to RAG1/2 activity. To elucidate control elements, we deleted the 100-kb intergenic region that separates the V(H) and D clusters (generating ΔV(H)-D alleles). In both B and T cells, ΔV(H)-D alleles initiated high-level antisense and, at lower levels, sense transcription from within the downstream D cluster, with antisense transcripts extending into proximal V(H) segments. In developing T lymphocytes, activated germ-line antisense transcription was accompanied by markedly increased IgH D-to-J(H) rearrangement and substantial V(H) to DJ(H) rearrangement of proximal IgH V(H) segments. Thus, the V(H)-D intergenic region, and likely elements within it, can influence silencing of sense and antisense germ-line transcription from the IgH D cluster and thereby influence targeting of V(D)J recombination.

Indexed as

AllelesAnimalsB-LymphocytesDNA-Binding ProteinsDNA, IntergenicGene Rearrangement, B-Lymphocyte, Heavy ChainGenetic LociHomeodomain ProteinsImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionMiceMice, Mutant StrainsRNA, AntisenseT-LymphocytesTranscription, GeneticDNA-Binding ProteinsDNA, IntergenicHomeodomain ProteinsImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionRAG-1 proteinRag2 protein, mouseRNA, Antisense

Identifiers

PMID21123744
PMCPMC3009784
OpenAlexW2022262778

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.